UB: Drug developed for Type 2 diabetes - in combination with insulin and liraglutide - helps control Type 1 diabetes

Submitted

Thu, Aug 4th 2016 02:25 pm

Dapaglifozin also helped some patients lose weight; two
patients developed ketones

By the University at Buffalo

University at Buffalo
endocrinologists who, in recent years, found patients with Type 1 diabetes
benefit from insulin plus a drug designed for Type 2 diabetes, have now found
they also can benefit from dapagliflozin, another drug designed and marketed to
treat Type 2 diabetes.

Today, researchers at the Jacobs
School of Medicine and Biomedical Sciences at UB published a paper online
ahead of print in the Journal of Clinical Endocrinology and Metabolism that
reports patients with Type 1 diabetes saw improved blood glucose control with a
"triple therapy" that included insulin, liraglutide and dapagliflozin.

Paresh Dandona, M.D., Ph.D.,
senior author on the paper, is SUNY Distinguished Professor and chief of
endocrinology, diabetes and metabolism in the department of medicine in the
Jacobs School of Medicine and Biomedical Sciences. He sees patients through
UBMD Internal Medicine at the Diabetes and Endocrinology Center of Western New
York, where the study was conducted.

Thirty people who had Type 1
diabetes participated in the randomized, placebo-controlled clinical trial.
Participants were between the ages of 18 and 75, and were already taking
liraglutide and insulin to manage their diabetes. Twenty participants were
randomly assigned to receive 10 milligrams of dapaglifozin daily for 12 weeks,
and the other 10 received a placebo during that period.

"Since liraglutide produces
improvements most impressively in patients with higher body mass index and
higher hemoglobin A1C, it is clear that we need other agents that act
independently of insulin, since Type 1 diabetics have no beta cells that
produce insulin," Dandona explained.

Hemoglobin A1C - patients' average
blood glucose over a 90-day period - declined by 0.66 percent among
participants who received the triple therapy, while there was no significant
change in the placebo group. Fourteen of the 17 people on the triple therapy
lost weight, with weight loss averaging four pounds. Patients in the placebo
group did not lose weight.

Twenty-six participants completed
the study. Two of the participants receiving the triple therapy developed
diabetic ketoacidosis, a dangerous complication that occurs when acids and
substances called ketones build up in the blood due to lack of insulin. This
occurred within two days of researchers increasing the daily dapagliflozin dose
to 10 milligrams from 5 milligrams. Both people were withdrawn from the study.

"Our data also show for the first
time that all patients on dapagliflozin experience an increase in ketones,"
Dandona said. "This may predispose people to developing diabetic ketoacidosis,
particularly among those who have a marked reduction in insulin from taking
liraglutide together with dapagliflozin, and who have consumed too few
carbohydrates. Our study sheds light on potential strategies for preventing
diabetic ketoacidosis, but more research is still needed in this area."

Dandona said these data suggest
insulin dose reductions should be minimized and that the higher dose of
dapagliflozin should not be used in such patients.

Founded in 1846, the Jacobs School of Medicine and Biomedical Sciences
at the University at Buffalo is beginning a new chapter in its history with the
largest medical education building under construction in the nation. The
eight-story, 628,000-square-foot facility is scheduled to open in 2017. The new
location puts superior medical education, clinical care and pioneering research
in close proximity, anchoring Buffalo's evolving comprehensive academic health
center in a vibrant downtown setting.

These new facilities will better enable the school to advance health
and wellness across the life span for the people of New York and the world
through research, clinical care and the education of tomorrow's leaders in
health care and biomedical sciences. The school's faculty and residents provide
care for the community's diverse populations through strong clinical
partnerships and the school's practice plan, UBMD Physicians' Group.